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Biomedical subjects

G M Mavligit

Publications and source records attributed to G M Mavligit.

At least 55 records · Page 3Linked to original sources
PubMed1982

Partial restoration of local GVH reaction in cancer patients by depletion of theophylline-sensitive suppressor T-cells.

Theophylline-resistant T-cell subpopulations were assessed in terms of numbers and function among patients with disseminated cancer, and compared to normal controls. Within the total E-rosetting T-cells (65 +/- 6.5% for normal donors versus 34 +/- 1.0% for cancer patients; P less than 0.001) the proportion of theophylline-resistant Te cells was 56 +/- 1.5% and 26.6 +/- 1.1%, respectively (P less than 0.001). This significant difference in distribution between theophylline-resistant (effector) and theophylline-sensitive (suppressor) cells in favor of the latter was also reflected by the poor performance of unseparated T-cells in the local GVH reaction. Thus, the mean GVH reaction among normal donors was 159 +/- 30 mm3 versus 44 +/- 28 mm3 among cancer patients (P less than 0.001). Removal of the theophylline-sensitive suppressor T-cells resulted in significant augmentation of the local GVH reaction among normal donors and in significant, although partial, immune restoration of the local GVH reaction in some patients but not in others. The mean local GVH reaction after removal of theophylline-sensitive suppressor T-cells was 196 +/- 89 mm3 among normal donors and 68 +/- 46 mm3 among cancer patients (P less than 0.05). This immune restoration following depletion of suppressor T-cells was only partial among cancer patients because of an apparent intrinsic defect in the capacity of their effector T-cells to exert vigorous local GVH reaction. In one small group of four patients, this intrinsic defect was so profound that even after removal of the theophylline-sensitive suppressor cells, the restoration of the local GVH reaction was negligible (12 +/- 10.8 mm3 versus 24 +/- 9.8 mm3; P greater than 0.1). The quantitative and qualitative changes in effector and suppressor T-cell distribution during the development of the malignant process and the possible interaction between them are discussed.

Animals↗
PubMed1982

Immunodiagnosis of human melanoma: characterization of human melanoma antigens and their detection in sera of melanoma patients by radioimmunoassay.

Double antibody radioimmunoassay (RIA), using radioiodinated melanoma-associated antigens (MAA), rabbit antiserum raised against 3 M KCl extract of human melanoma (AHMS) and goat antirabbit IgG antibody, was employed for the detection of MAA in tumors as well as in sera of melanoma patients. MAA were partially purified from crude KCl extract of melanoma tissue by affinity column chromatography using AHMS and concanavalin A. A high content of MAA was detected in all but one melanoma extract, while normal tissue and nonmelanoma tumor extracts contained MAA to a much lesser extent than did melanoma extracts. MAA were also found in melanoma patients' sera (20/45) but not in sera of normal donors (0/10) and colon cancer patients (0/10). Immunochemical data suggest that AHMS-defined MAA consist of two major glycoproteins with molecular weights of 37K and 31K daltons, which does not cross-react either with carcinoembryonic antigen or beta 2-microglobulin or with BCG.

Antigens, Neoplasm↗
PubMed1981

Intraarterial cis-platinum for patients with inoperable skeletal tumors.

Twenty-three patients with inoperable skeletal tumors were treated with intraarterial cis-platinum prior to attempted surgery. The antitumor effect of intraarterial cis-platinum was monitored clinically by radiologic imaging techniques, and whenever possible, evaluated histopathologically by examinatin of surgical or biopsy tumor specimens. Objective responses were noted in 12 patients (52%) and included 2 complete, 7 partial and 3 less-than-partial remissions lasting from 14 to 70 weeks. Limb-saving surgery or hemipelvectomy became subsequently feasible in four and one patients respectively. Preoperative intraarterial cis-platinum is a safe procedure which might be used effectively in combination with other, more conventioal postoperative adjuvant chemotherapy against skeletal tumors.

Bone Neoplasms↗
PubMed1981

The palliative role of hepatic arterial infusion and arterial occlusion in colorectal carcinoma metastatic to the liver.

Fifty-five patients with metastatic colorectal carcinoma confined to the liver were treated with hepatic arterial infusion of floxuridine and mitomycin C. Tumour response rate was 43.4% and median overall survival was 11 months. Prolonged survival was associated with intentional or inadvertent occlusion of the hepatic artery. The median survival of twenty-four patients with arterial occlusion (15 months) was significantly higher than that of thirty-one patients without arterial occlusion (8 months).

Antineoplastic Agents↗
PubMed1981

Immune restoration and/or augmentation of local xenogeneic graft versus host reaction by Cimetidine in vitro.

The immunorestorative effect of Cimetidine in vitro on the T cell-induced local GVH reaction in vivo was studied in 43 cancer patients and 43 normal healthy donors. Both low dose (10(-5) M) and high dose (10(-4) M) Cimetidine induced significant, albeit partial, immune restoration among GVHR-negative cancer patients (p less than 0.05, p less than 0.01, respectively) with the high dose being significantly more effective (p less than 0.05). In contrast, similar Cimetidine doses induced only moderate augmentation (p greater than 0.05) among GVHR-positive cancer patients and a marginal one among normal healthy donors. In the latter 2 groups, Cimetidine was found to be occasionally detrimental in that it induced a conversion from a positive to a negative GVH reaction. These results support the concept of anti-suppressor cell activity ascribed to Cimetidine. However, the possibility of a detrimental effect should be born in mind in planning future clinical trials. We propose that the use of Cimetidine be limited to cancer patients with documented increase in suppressor cell activity associated with defective T cell function under close serial monitoring.

Cimetidine↗
PubMed1980

Cellular immune modulation after a single high dose of Levamisole in patients with carcinoma.

The effect of a single high dose of Levamisole (200 mg/M2) on delayed-type hypersensitivity (DTH) in vivo and on lymphocyte blastogenesis to mitogens and antigens in vitro was studied in 26 patients with carcinoma. Similar studies were conducted in 24 control patients. Levamisole had a moderate but significant enhancing effect on DTH to Dermatophytin detectable no earlier than eight hours and still present at 48 hours after the drug administration. A moderate but significant enhancing effect on lymphocyte blastogenesis to mitogens and antigens was also demonstrated during the same time sequence. Further clinical trials with Levamisole should be conducted with more attention paid to schedule of drug administration.

Breast Neoplasms↗
PubMed1980

Percutaneous hepatic arterial infusion (HAI) of mitomycin C and floxuridine (FUDR): an effective treatment for metastatic colorectal carcinoma in the liver.

The response rate of metastatic colorectal carcinoma confined to the liver to HAI of FUDR alone is at the range of 50% and to mitomycin C by hepatic arterial infusion (HAI) at the range of 35%. Mitomycin C was added to FUDR by continuous infusion and given by HAI to 12 patients with colorectal cancer confined to the liver. Catheters were placed subselectively in the hepatic artery, and infusion continued for five to six days when the catheter was removed. Cycles were repeated every 30 days. Chemotherapy consisted of mitomycin C 15 mg/m2 administered on day 1 followed by FUDR 100 mg/m2 by continuous infusion daily for five days. Response to treatment was evaluated by serial determinations of plasma CEA and by imaging techniques consisting of a computerized tomography, sonography, and radionuclide scanning of liver as well as by angiography. In 2 patients, complete remission was achieved; in 4 patients a 75% and in another 4 patients a 50% decrease in liver metastasis was observed, while 2 patients had stable disease. Thus, a response rate of 83% with a median duration of six to seven months was achieved. The median survival of the these patients was 16 months. Eight of the 12 patients have failed previous, i.v. 5-FU containing regimens. Complications related to 45 treatment cycles were the following: catheter displacement in 11.1%, an intimal tear, usually in the hepatic artery in 4.4%, gastric ulcerations in 5.4%, and septicemia in 2.7% of the cycles. In addition, aneurysmal dilation of the hepatic artery occurred in 4 patients (8.8% of the treatment cycles), all of whom continued treatment. Chemotherapy-related complications included primarily thrombocytopenia and stomatitis. Mitomycin C + FUDR by hepatic arterial infusion is an effective treatment for colorectal carcinoma metastatic to the liver. The high response rate justifies the adjuvant treatment of Dukes class C colon cancer patients with this treatment.

Adult↗
PubMed1980

Phase I-II trial of percutaneous intra-arterial cis-diamminedichloro platinum (II) for regionally confined malignancy.

Forty-nine patients with regionally confined recurrent malignancy were treated with intra-arterial cis-diamminedichloro platinum II in a Phase I-II trial. A safe starting dose of 120 mg/m2 was established. An overall response rate of 45% was noted with significant responses observed among patients with melanoma, sarcoma, breast carcinoma, and neuroblastoma. Side effects included transient renal and bone marrow toxicity as well as neurotoxicity and ototoxicity (6%), the latter usually with residual damage. The rational basis and advantages of treatment with intra-arterial cis-platinum are discussed.

Adolescent↗
PubMed1980

Cyclic nucleotide alterations in mixed leukocyte reaction: a preliminary report.

Endogenous cyclic adenosine and guanosine monophosphate (cAMP, cGMP) levels were studied in human peripheral blood lymphocytes during mixed leukocyte reactions (MLR). cAMP level was consistently elevated in one-way MLR, with good correlation to 3H-thymidine uptake in these reactions. In contrast, cGMP level was practically unchanged. Irradiation of reacting cell populations resulted in inhibition of cyclic nucleotide phosphodiesterase (PDE) activity. These results suggest that metabolic alterations in cAMP may be associated with immune reactions of cellular recognition.

Cyclic AMP↗
PubMed1980

Indomethacin-induced, monocyte-dependent restoration of local graft-versus-host reaction among cells from cancer patients.

Peripheral blood mononuclear cells from 16 of 17 cancer patients known to have a negative local graft-versus-host (GVH) reaction (T-cell function deficiency) were pharmacologically immunorestored by treatment with indomethacin. The restorative effect of the indomethacin was exerted directly on nonadherent lymphocytes. This process of desuppression required for its completion the presence of glass-adherent monocytes. The immune restorative effect of indomethacin in terms of local GVH reaction did not appear to be mediated by inhibition of prostaglandin synthesis. Pharmacologic immune restoration may be an important therapeutic modality in cancer patients.

Animals↗
PubMed1980

Surface antigenic characteristics of human melanoma cells defined by xenoantiserum raised against papain-solubilized melanoma-associated antigens.

Xenoantiserum to human malignant melanoma was prepared by immunizing rabbits with melanoma associated antigens (MAA) solubilized from melanoma cell membrane by limited papain digestion. The antiserum was absorbed extensively with red cells, leukemia cells and cultured lymphoid cell lines, and was assayed for its reactivity with different human cell types by the indirect membrane immunofluorescence and radioimmunoprecipitation techniques. The data obtained suggest that there are at least two different MAA on human melanoma cells. The first is melanoma-group specific and can be detected commonly on different melanoma cell lines. The second is oncofetal and is shared by melanoma, carcinoma, and fetal cells tested thus far. Immunoprecipitated material from melanoma cell membrane that had been radioiodinated with lactoperoxidase and solubilized with a non-ionic detergent was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which showed two major peaks with estimated molecular weights of 90,000 and 120,000 daltons. The 90,000 molecular weight component appears to be oncofetal, as it disappeared when the antiserum was absorbed with either melanoma or carcinoma cell lines.

Animals↗
PubMed1979

Receptor sites for complement and for immune complexes on human nonhemopoietic tumor cells.

Tumor cells in primary cultures derived from 11 untreated nonhemopoietic cancer patients were reacted with specifically coated sheep erythrocytes. Rosette formation between tumor and indicator cells was assessed, Eight of the primary cultures reacted positively with both IgG-coated (EAIgG) and with IgM-human complement coated (EAIgMC or EAIgMC 4,3) sheep erythrocytes. EAIgG rosette formation in positive cultures ranged from 25 to 85%, and for EAIgMC/EAIgMC 4,3 reactivity ranged between 22--95%. Rosette formation with E (uncoated) and EAIgM was negligible. These findings suggest that human nonhemopoietic tumor cells may carry on their surface receptor sites for an IgG component of immune complexes and for human complement. These receptor sites may be important in the host-tumor relationship.

Adenocarcinoma↗
PubMed1979

Immunotherapy with levamisole: early decrease of cAMP levels in lymphocytes from treated cancer patients.

Lymphocyte cyclic nucleotide content was studied before and after Levamisole administration to cancer patients. Twelve patients with disseminated cancer received 100 mg/m2 on two consecutive days; nine comparable patients with disseminated cancer served as controls. Endogenous cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured in lymphocytes before, 24, and 48 hours after ingestion of the first dose of Levamisole. A statistically significant decline in lymphocyte cAMP level was observed after drug administration and no significant changes were noted in cGMP levels. Further studies will be necessary to correlate this biochemical change in cyclic nucleotides with modulation of the functional level of cellular immune mechanisms.

Breast Neoplasms↗
PubMed1979

The use of leukocyte cell line culture supernatant for skin reaction testing in malignant melanoma.

A study was conducted to determine some of the potential applications of a human leukocyte culture supernatant or "lymphokine" preparation in cancer patients. The application evaluated in this study was the use of this preparation as a skin test reagent for evaluation of the inflammatory response following intradermal injection. The preparation was derived from the supernatant of a long-term cultured lymphoblastoid cell line with migration inhibition factor (MIF) and other lymphokine activities. Dose response, histology and toxicity studies were done in 53 patients with malignant melanoma stage IIIB and IV. A dose response curve was observed for both erythema and induration at 12 and 24 hours, but not at 48 hours. An optimal intradermal dose for eliciting inflammation was determined and found to be five units. Histopathological evaluation of biopsy specimens showed a mixed cell reaction including granulocytes, eosinophils, lymphocytes and monocytes differing in lymphocyte content from the classical delayed type hypersensitivity (DTH) reaction in man. Compared with the response to recall antigens, only a weak correlation with the DTH response to the recall antigens was found. Our results support the conclusion that lymphokines may be used in the future to evaluate the ability to develop nonspecific inflammation in cancer patients, and that this inflammatory response can be obtained in a number of patients no longer capable of responding to recall antigens.

Adult↗
PubMed1979

Adenocarcinoma of unknown primary site: a clinico-pathological study.

An analysis of the clinico-pathological findings in 49 patients with adenocarcinoma of unknown primary origin indicates a short survival time. No factors were identified that influenced survival. Thromboembolic episodes and second primary tumors commonly complicate the clinical course. Metastases in widespread organs are common autopsy findings. Immunological mechanisms may explain these findings.

Abdominal Neoplasms↗